EBMT 2026 | The importance of molecular diagnosis of germline leukemias

So germline leukemias are an entity that has been recognized in the recent 10 years, in the recent decade, thanks to the application of the new molecular tools and the discovery of numerous gene mutations which are germane to the disease pathobiology, in particular of MDS and AML. In general, in all comers of MDS and AML, 5 to 10 percent are individuals who carry or might carry a germline trait. And this has been something that has been recently growing thanks to the application of this NGS platform in the diagnostics, thanks also to the new guidelines regarding the genomic profiling of both these disorders, MDS and AML. 

One of the key aspects is that recognizing the presence of germline predisposition is important in clinical practice for the management of the patient. We are at the EBMT and of course this is like a crucial aspect for transplant because of potential adjustment of conditioning regimens in particular in cases with DNA repair genes mutation or donor choice. If we identify a genomic mutation which is a germline, we need to segregate the variant within the family in order to understand if we can use a related donor or not. And therefore it is important to always have a multidisciplinary team involving also a human geneticist in our institution, for instance, we have a combined clinic and therefore assess the patient from both the hematologic and the human genetic constitutional point of view in order to have also counseling for a family, which needs to be guided through the process of a diagnosis which is somehow like a Damocles sword in the families of this patient which previously didn’t know that perhaps an increased risk of leukemia was present or may be present in the family. Therefore it’s also important to always have psychological support for these patient and of course this raises the question of a lot of ethical concerns also for the unrelated donors that we use for allogeneic transplantation because the donors need to be consented and yesterday was a very lively session on these, trying to understand what we can do internationally with our societies in order to have a unified framework to protect donors with regards especially to the presence of potential germline variants in these donors.

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